chr10-92634645-T-G

Variant names:

• chr10-92634645-T-G
• rs10882095
• NM_004523.4:c.1875+850T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004523.4(KIF11):​c.1875+850T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,076 control chromosomes in the GnomAD database, including 8,252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8252 hom., cov: 32)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 4 publications found

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004523.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	NM_004523.4	MANE Select	c.1875+850T>G		intron	N/A	NP_004514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000260731.5	TSL:1 MANE Select	c.1875+850T>G		intron	N/A	ENSP00000260731.3	P52732
	KIF11	ENST00000937278.1		c.1875+850T>G		intron	N/A	ENSP00000607337.1
	KIF11	ENST00000676647.1		c.1668+850T>G		intron	N/A	ENSP00000503394.1	A0A7I2V3A9

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47172 AN: 151958 Hom.: 8250 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47191 AN: 152076 Hom.: 8252 Cov.: 32 AF XY: 0.315 AC XY: 23401 AN XY: 74322

African (AFR) AF: 0.175 AC: 7247 AN: 41516

American (AMR) AF: 0.262 AC: 3995 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1229 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3482 AN: 5170

South Asian (SAS) AF: 0.470 AC: 2267 AN: 4826

European-Finnish (FIN) AF: 0.392 AC: 4134 AN: 10540

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23615 AN: 67960

Other (OTH) AF: 0.321 AC: 680 AN: 2116

Alfa AF: 0.311 Hom.: 1017

Bravo AF: 0.298

Asia WGS AF: 0.507 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	18
DANN	Benign	0.61
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.46		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10882095; hg19: chr10-94394402;